Protein tyrosine phosphatases (PTPs) belong to signal-transduction enzymes. They regulate cell growth, differentiation and metabolism by modulating the phosphorylation level of intracellular tyrosine. PTPs also regulate cell migration, genetic transcription, opening and closing of an ion channel, immune response, apoptosis and osteoblastic development. PTPs disorder may result in a variety of diseases such as cancer, diabetes, obesity and osteoporosis. To date, there has been found more than 130 gene-encoding PTPs in human genome. These highly specific PTPs are not only associated with the signal pathway of the inhibition and occurrence of cancers, but can also directly lead to the onset of different diseases in human due to their dysfunctions. The action mechanisms of PTPs associated with the onset of diseases as well as the screening of their inhibitors are always the hot focus of the word.
PTPases which include a large family of transmembrane (receptor type) and intracellular (non-receptor type) enzymes are involved in regulation of a series of vital life processes. Several PTPases may affect the action of insulin at the receptor or post-receptor stage in the insulin pathway. Currently, studies mainly focus on the research of SHP-2 and PTP1B.
PTP1B is the first protein tyrosine phosphatase that has been successfully isolated. This enzyme is an intracellular enzyme of 37 kD. It anchors onto the endoplasmic reticulum via the 35 amino acid residues-containing C-terminal. Cysteine at the 215th position is the catalytic active site of PTB1. Studies have shown that PTP1B blocks the signal transduction pathway of insulin via Insulin Receptor (IR) and Insulin Receptor Substrate (IRS) and ultimately affects the transportation of glucose from blood into cells, which represents as an elevated blood glucose. In addition, since PTP1B gene knockout mice are immune to obesity, it can be determined definitely that PTP1B plays a key role in the pathogenesis of obesity. Consequently, PTP1B is a target of the development of new medicaments for the treatment of diabetes and obesity.
Protein tyrosine phosphatase SHP2 [Src homology 2 (SH2) domain containing phosphotyrosinephosphatase 2] is a non-receptor type protein tyrosine phosphatase (PTP) which is encoded by PTPN11 gene and widely expressed in cytoplasm. SHP2 plays a key role in processes such as cell proliferation and differentiation by participating in a variety of intracellular signal transductions, such as MAP kinase pathway, Jak-Stat pathway, PI3 kinase pathway and other pathways. PTPN11 is identified as a proto-oncogene and also involves in the signal pathways of many other proto-oncogenes as an important member. Hence, SHP2 serves as a potential drug target for the treatment of diseases such as Noonan syndrome and juvenile myelomonocytic leukemia, as well as other possible relevant tumor diseases.
Up to date, there is no report yet available in the prior art concerning the extraction of a protein tyrosine phosphatase inhibitor from the fermentation product of Isaria Fumosorosea Wize.